The objective of this project is to determine basic mechanisms of how the transformed state is expressed phenotypically in terms of the regulation of cell proliferation and surface characteristics important to growth control The projects are designed to focus on the plasma membrane and cell surface as a major locus of growth control and site of expression of the transformed phenotype, not as an isolated series of events, but in the context of an integrated cellular system where provision is made for eventual contributions to understanding the exchange of information between the nucleus and the cell surface in the form of cell surface/cytoplasm and nucleus/cytoplasm interactions. The results of these studies are expected to advance our understanding of the control of cell proliferation and of the biochemical events critical to the expression of the transformed phenotype including altered growth rates, loss of adhesion, failures in contact inhibition mechanisms and acquisition of invasive potential. These studies will be explored in cellular systems common to all projects which make primary use of liver lines temperature sensitive for expression of the transformed phenotype. Experiments will be extended to cell-free systems as rapidly as they can be developed for examination of detailed mechanisms. In addition, we anticipate that the studies will add to the body of knowledge concerning events important to tumor induction, promotion, and progression and ultimately provide new biochemical targets for the development of strategies of chemoprevention or therapy of possible clinical importance. (A)